Chili peppers contain the chemesthetic agent capsaicin, which is one of the best-known activators of the TRPV1 (transient receptor potential vanilloid) receptor. Humans describe the sensations from capsaicin as hot, burning and stinging and in the laboratory, heavy chili users report less burn compared to non-users. Desensitization can be induced following repeated capsaicin exposure and unlike adaptation to odorants or tastants, can be chronic, lasting across days. The mechanism behind chronic desensitization is poorly understood. TRPV1 activation releases substance P, a neuropeptide associated with pain and inflammation, but simple depletion of substance P cannot explain chronic desensitization. Research in animal models suggests capsaicin exposure may result in down-regulation of TRPV1 expression; whether a similar effect is seen in humans is unknown. In humans, expression of TRPV1 mRNA has been linked with burning mouth syndrome and oral cancer, showing up-regulation in lingual tissues. As very little is known about the effect of chronic oral exposure to capsaicin on the expression and regulation of TRPV1 in human fungiform papillae, this proposal has been developed in bridge the gap regarding TRPV1 expression in humans and animal studies which show capsaicin exposure reduces TRPV1 expression. Here, we hypothesize that chronic capsaicin desensitization in humans is due to a decrease in TRPV1 expression. Therefore, the first aim of the proposed research is to determine if TRPV1 expression in fungiform papillae is associated with capsaicin sensitivity and burn intensity. The second aim will determine if TRPV1 is down regulated as a response to repeated capsaicin oral exposure, as would occur in a high chili containing diet. The third aim will determine the extent of repeated capsaicin exposure on the perceptual responses to capsaicin. To test these aims, sixty participants meeting inclusion criteria will be recruited from the Penn State campus and assigned to either a treatment or control group. Over a 21 day treatment period, participants will swish once per day with a mouthwash of 2ppm capsaicin (treatment group) or 20uM sucrose octaacetate (control group). Psychophysical measurements and fungiform papillae collection will be conducted before, during and after the treatment period. Psychophysical methods include suprathreshold ratings from capsaicin and other control stimuli, and capsaicin detection thresholds. The findings from this research may demonstrate a link between low dose oral capsaicin exposure and reduced TRPV1 expression, which may ultimately lead to new therapies or treatment options for patients with oral pathologies associated with altered TRPV1 expression, including burning mouth syndrome or oral cancer. These findings may provoke additional research that translates to other chronic inflammatory diseases such as irritable bowel syndrome. The potential